Several monoclonal antibodies have been evaluated for their reactivity to benign and malignant serous effusions using immunohistochemical techniques. Monoclonal B72.3 which is reactive against a 220,000-400,000 d glycoprotein complex was uniformly reactive with malignant effusions containing adenocarcinoma of the breast, ovary and lung. This monoclonal antibody was routinely negative with squamous cell carcinoma, lymphoma, leukemia and benign effusions. Other monoclonal antibodies exhibited staining which did not differentiate mesothelium from carcinoma. The preliminary results of this study present evidence that monoclonal antibody B72.3 may function as a highly selective marker in recognizing a cancer cell versus a mesothelial cell, and an adenocarcinoma cell versus other malignant tumor cells.